2. Academic Validation
  3. Polymer-based gene-drug co-delivery system effectively inhibits pathologic retinal neovascularization through dual anti-inflammatory and anti-neovascular actions

Polymer-based gene-drug co-delivery system effectively inhibits pathologic retinal neovascularization through dual anti-inflammatory and anti-neovascular actions

  • Biomaterials. 2025 Sep 3:326:123680. doi: 10.1016/j.biomaterials.2025.123680.
Mengtian He 1,  Dayang Xie 2,  Qiannan Cao 2,  Mingxia Jiang 2,  Hongqian Liu 2,  Yingli Yao 2,  Wenming Zheng 2,  Huilin Yuan 2,  Pijun Su 2,  Siting Zhang 2,  Yuxuan He 1,  Shuting Zeng 2,  Yaqing Zeng 2,  Huapan Fang 3,  Hong Wu 4,  Huayu Tian 2
Affiliations

Affiliations

  • 1 Department of Ophthalmology, The Second Hospital of Jilin University, Changchun 130041, China.
  • 2 State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), Xiamen University, Xiamen 361005, China.
  • 3 State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), Xiamen University, Xiamen 361005, China; Shenzhen Research Institute of Xiamen University, Shenzhen 518000, China. Electronic address: [email protected].
  • 4 Department of Ophthalmology, The Second Hospital of Jilin University, Changchun 130041, China. Electronic address: [email protected].
PMID: 40916239 DOI: 10.1016/j.biomaterials.2025.123680
Abstract

Retinal neovascularization is one of the most prevalent fundus neovascular diseases, affecting vision and potentially leading to severe complications, such as retinal detachment or irreversible blindness. Current treatments primarily involve intravitreal injections (IVT) of anti-vascular endothelial growth factor (anti-VEGF) agents. However, such treatment often requires repeated injections, develop incomplete responses, and are associated with adverse effects. Therefore, novel therapeutic agents need to be developed that exhibit low side effects and improved therapeutic efficacy of retinal neovascularization. Herein, we develop a novel polymeric gene carrier, phenylboronic acid-modified linear polyethylenimine (LPEI-PBA) that is capable of loading plasmid expressing short hairpin RNA (pshVEGF), which self-assembles with dexamethasone sodium phosphate (DSP) via electrostatic interactions to form a polymer-based gene-drug co-delivery system (DSP/LPEI-PBA/pshVEGF, DPPV) for combined neovascularization inhibition. DSP not only exerts anti-inflammatory effects but also enhances the transfection efficiency of LPEI-PBA. DPPV demonstrated favorable anti-neovascular effects both in vitro and in vivo. In an oxygen-induced retinopathy model, a single intravitreal administration of DPPV can significantly inhibited pathological neovascularization, accompanied by the downregulation of glial activation markers glial fibrillary acidic protein (GFAP) and ionized calcium-binding junction molecule 1 (IBA-1), as well as the pro-inflammatory factor interleukin-1β (IL-1β), and the upregulation of the anti-inflammatory factor ARG-1. In conclusion, DPPV nanoparticles effectively inhibit pathological retinal neovascularization through dual anti-inflammation and anti-angiogenesis, showing a promising therapeutic option for fundus neovascularization diseases.

Keywords

Anti-Angiogenesis; Anti-inflammation; Polymer-based gene-drug co-delivery system; Retina neovascularization.

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